馬麗秋　王閏　于濤　劉光耀　龔海東　王麗穎

[關(guān)鍵詞] 高血壓;抗高血壓藥物;藥物基因組學(xué);基因多態(tài)性

[中圖分類號] R544.1? ? ? ? ? [文獻(xiàn)標(biāo)識碼] A? ? ? ? ? [文章編號] 1673-9701（2021）22-0188-05

Research progress on gene polymorphism of antihypertensive drugs

MA Liqiu1? ?WANG Run1? ?YU Tao1? ?LIU Guangyao1? ?GONG Haidong1? ?WANG Liying2

1.Department of Neurosurgery，Hongqi Hospital Affiliated to Mudanjiang Medical College， Mudanjiang? ?157000，China;

2.Department of Neurology，Hongqi Hospital Affiliated to Mudanjiang Medical College， Mudanjiang? ?157000，China

[Abstract] Hypertension is one of the most relevant risk factors for cardiovascular disease，and its prevalence continues to rise worldwide，but it cannot be cured according to current medical treatments.The main treatment for hypertension is the use of antihypertensive drugs to control blood pressure，improve symptoms and reduce complications.At present，great progress has been made in the research on gene polymorphisms of antihypertensive drugs.It has been found that some gene polymorphisms have an impact on the metabolism and efficacy of antihypertensive drugs，such as angiotensin II receptor，cytochrome P450，etc.Genetic testing technology has been used by clinicians to guide patients in medication，which has greatly improved the therapeutic effect of hypertension.In-depth study of gene polymorphisms of antihypertensive drugs and discovery of new targets that affect the effects of antihypertensive drugs are of great significance for improving existing antihypertensive drugs and developing new and more effective antihypertensive drugs.This article reviews the related gene polymorphisms of five types of antihypertensive drugs commonly used in hypertension，and provides new insights for precise treatment and individualized treatment of hypertension patients.

[Key words] Hypertension;Antihypertensive drugs;Pharmacogenomics;Gene polymorphism

高血壓是多種循環(huán)系統(tǒng)疾病最主要的危險(xiǎn)因素，易并發(fā)腦卒中和心力衰竭等多種高風(fēng)險(xiǎn)疾病。根據(jù)2015年的調(diào)查結(jié)果顯示，全球高血壓患者約11.3億人，其中因收縮壓>140 mmHg而導(dǎo)致患者死亡的死亡率約為106.3/10萬，我國高血壓患病率約為23%、控制率約為15%、知曉率約為47%[1-2]，控制率明顯低于美國等發(fā)達(dá)國家。

高血壓主要依靠藥物治療，但藥物效果差異較大，這與患者的身體健康狀態(tài)、遺傳因素、病因、年齡等多種因素相關(guān)。研究表明，藥物代謝酶、轉(zhuǎn)運(yùn)蛋白和相關(guān)藥物作用受體變異是藥效差異的主要原因[3]，部分患者藥物療效差，甚至出現(xiàn)嚴(yán)重的不良反應(yīng)。

1 高血壓相關(guān)基因研究概述

高血壓的致病因素主要包括遺傳和環(huán)境，而遺傳因素的影響較大，針對高血壓患者遺傳因素的研究表明，遺傳因素導(dǎo)致的血壓差異約占30%～50%，遺傳因素不僅與高血壓有關(guān)，也與降壓治療的效果有關(guān)[4]。單基因遺傳性高血壓包含Gordon綜合征、先天性腎上腺皮質(zhì)增生癥、Liddle綜合征等。原發(fā)性高血壓為多種基因共同致病，對于高血壓致病基因、血壓變化相關(guān)基因和影響藥物治療效果基因進(jìn)行研究已成為熱點(diǎn)。研究發(fā)現(xiàn)，白介素10和內(nèi)皮型一氧化氮合酶（Endothelial nitric oxide synthase，eNOS）均可以明顯的降低血壓[5-6]。Li等[7]根據(jù)加權(quán)基因共表達(dá)網(wǎng)絡(luò)分析發(fā)現(xiàn)miR-548am-3p、miR-513c-3p、miR-182-5p、miR-548d-5p、IGF1R、GSK3B、FOXO1、PRKAR2B、HIF1A、PIK3R1均與高血壓相關(guān)。目前，已經(jīng)發(fā)現(xiàn)約120個(gè)基因與高血壓的致病性和藥物敏感性等特性相關(guān)，其中約有26個(gè)基因可以進(jìn)行深入研究，具有一定的靶向治療潛力[8]。